PROJECT SUMMARY: The Scripps Research Institute Molecular Screening Center (SRIMSC) at Scripps Florida is requesting funds for the purchase of a kinetic imaging plate reader as a replacement for its current Molecular Devices (MD) Fluorometric Image Plate Reader (FLIPR) TETRA. Kinetic plate readers are designed to study cellular signaling processes and are an essential component to many High Throughput Screening (HTS) facilities that implement 384-well and 1536-well micro-well plate technology. Although the current FLIPR TETRA has been an outstanding instrument, it has served SRIMSC for nearly 12-years (installed: Dec 29, 2005) and is past its life-expectancy. The SRIMSC seeks funds to purchase a replacement Molecular Devices FLIPR TETRA in order to continue providing full HTS support to Scripps Research faculty and the broader NIH research community as a whole. Fluorometric Image Plate Readers are designed to study cellular signaling processes through simultaneous and parallel fluorescence readouts across an entire multi-well plate (i.e. 96w, 384w, 1536w formats). Common assays used on kinetic imaging plate readers are fluorescence/luminescence-based and measure membrane potential changes (ion channels), intracellular calcium dynamics, GPCR signaling, cyclic nucleotide activation and enzymatic substrate conversions. Since establishing HTS operations in 2005, SRIMSC has screened over 84 large library FLIPR-based campaigns. Indeed, ~28% of the HTS screening activities to date have required the use of a kinetic plate reader. The SRIMSC served as one of four comprehensive HTS centers commissioned by the NIH during the MLPCN program (2005-2013). In this MLPCN era, the FLIPR supported 145 HTS screenings (validation, primary, secondary?) on over 20 unique biological targets; many with multi-modal activities (i.e. agonists, inverse agonists, biased agonists, antagonists, positive allosteric modulators), all resulting in publication of some form. It is crucial that this instrument is replaced in a timely fashion to avoid crippling ongoing NIH-funded activities and hindering research programs aimed at advancing basic and translational research. Since the SRIMSC implements 1536- well HTS as a cost-effective format for large library testing, it requires a Fluorometric Image Plate Reader that can handle these higher well density plates. Only two instrument vendors provide such a device: Molecular Devices (FLIPR TETRA) and Hamamastu (FDSS-7000). After careful consideration, it was deemed most prudent and cost-effective to select the MD FLIPR TETRA as the replacement choice. In summary, the timely replacement of the outdated MD FLIPR TETRA, at its end of service-life, with a new instrument well help ensure that SRIMSC HTS services can meet its future obligations by providing uninterrupted HTS support for drug discovery efforts for the NIH supported community.